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Diaryltriazine non-nucleoside reverse transcriptase inhibitors are potent candidates for pre-exposure prophylaxis in the prevention of sexual HIV transmission

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dc.contributor.author Ariën, K. K. en_US
dc.contributor.author Venkatraj, M. en_US
dc.contributor.author Michiels, J. en_US
dc.contributor.author Joossens, J. en_US
dc.contributor.author Vereecken, K. en_US
dc.contributor.author Van der Veken, P. en_US
dc.contributor.author Abdellati, S. en_US
dc.contributor.author Cuylaerts, V. en_US
dc.contributor.author Crucitti, T. en_US
dc.contributor.author Heyndrickx, L. en_US
dc.contributor.author Heeres, J. en_US
dc.contributor.author Augustyns, K. en_US
dc.contributor.author Lewi, P. J. en_US
dc.contributor.author Vanham, G. en_US
dc.date.accessioned 2014-09-25T13:39:47Z
dc.date.available 2014-09-25T13:39:47Z
dc.date.issued 2013 en_US
dc.identifier.issn 0305-7453 en_US
dc.identifier.doi http://dx.doi.org/10.1093/jac/dkt166 en_US
dc.identifier.other ITG-B1A; ITG-B3B; ITG-B5B; ITG-C7A; ITG-C8A; ITG-C9A; ITG-B10A; ITG-BLA; MULTI; DBM; U-VIROL; DCS; U-ARLAB; JIF; DOI; Abstract; UPD56 en_US
dc.identifier.uri http://hdl.handle.net/10390/7880
dc.description.abstract OBJECTIVES: Pre-exposure prophylaxis and topical microbicides are important strategies in the prevention of sexual HIV transmission, especially since partial protection has been shown in proof-of-concept studies. In search of new candidate drugs with an improved toxicity profile and with activity against common non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV, we have synthesized and investigated a library of 60 new diaryltriazine analogues. METHODS: From this library, 15 compounds were evaluated in depth using a broad armamentarium of in vitro assays that are part of a preclinical testing algorithm for microbicide development. Antiviral activity was assessed in a cell line, and in primary human cells, against both subtype B and subtype C HIV-1 and against viruses resistant to therapeutic NNRTIs and the candidate NNRTI microbicide dapivirine. Toxicity towards primary blood-derived cells, cell lines originating from the female reproductive tract and female genital microflora was also studied. RESULTS AND CONCLUSIONS: We identified several compounds with highly potent antiviral activity and toxicity profiles that are superior to that of dapivirine. In particular, compound UAMC01398 is an interesting new candidate that warrants further investigation because of its superior toxicity profile and potent activity against dapivirine-resistant viruses. en_US
dc.language English en_US
dc.subject Viral diseases en_US
dc.subject HIV en_US
dc.subject AIDS en_US
dc.subject Disease transmission-sexual en_US
dc.subject Prevention en_US
dc.subject Drug development en_US
dc.subject Pre-exposure en_US
dc.subject Prophylaxis en_US
dc.subject Microbicides en_US
dc.subject Non-nucleoside en_US
dc.subject Reverse transcriptase inhibitors en_US
dc.subject Diaryltriazine en_US
dc.subject Evaluation en_US
dc.subject In vitro en_US
dc.subject Assays en_US
dc.subject Subtype B en_US
dc.subject Subtype C en_US
dc.subject Dapivirine en_US
dc.subject Toxicity en_US
dc.title Diaryltriazine non-nucleoside reverse transcriptase inhibitors are potent candidates for pre-exposure prophylaxis in the prevention of sexual HIV transmission en_US
dc.type Article en_US
dc.citation.issue 9 en_US
dc.citation.jtitle Journal of Antimicrobial Chemotherapy en_US
dc.citation.volume 68 en_US
dc.citation.pages 2038-2047 en_US
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/23645585 en_US
dc.citation.jabbreviation J Antimicrob Chemother en_US


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